褪黑素对癫痫大鼠海马氧化应激及神经元凋亡的影响  

Effects of Melatonin on Oxidative Stress and Neuronal Apoptosis in Hippocampus of Rats with Epilepsy

作　　者：伍丽娜[1,2] 甘彦峰[3] 苏炳银[1,2] 

机构地区：[1]发育与再生四川省重点实验室,四川成都市610081 [2]成都医学院人体解剖与组织胚胎学教研室,四川成都市610081 [3]四川大学华西医院西藏成办分院,四川成都市610000

出　　处：《中国康复理论与实践》2016年第5期535-539,共5页Chinese Journal of Rehabilitation Theory and Practice

基　　金：发育与再生四川省重点实验室基金(No.SYS10-005);成都医学院校基金(No.CYZ14-009)

摘　　要：目的探讨褪黑素对癫痫大鼠海马氧化应激及神经元凋亡的影响及其机制。方法成年雄性Sprague-Dawley大鼠72只等分为对照组、模型组、褪黑素低剂量组和褪黑素高剂量组。模型组侧脑室注射马桑内酯50μg/kg,褪黑素低、高剂量组分别于腹腔注射褪黑素20 mg/kg和60 mg/kg后30 min,侧脑室注射马桑内酯50μg/kg。癫痫持续60 min后,采用紫外分光光度计检测丙二醛(MDA)、超氧化物歧化酶(SOD)的含量;原位末端标记法(TUNEL法)检测大鼠海马CA3区神经元凋亡;电镜观察海马CA3区神经元及其线粒体改变。结果与对照组相比,模型组海马神经元、线粒体出现明显超微结构损伤,凋亡细胞数显著增多(P<0.001),海马SOD显著降低(P<0.001),MDA显著升高(P<0.001)。与模型组相比,褪黑素低剂量组大鼠海马神经元、线粒体超微结构损伤有所改善,凋亡细胞数明显减少(P<0.01),SOD升高(P<0.05),MDA降低(P<0.05);褪黑素高剂量组大鼠海马神经元、线粒体超微结构损伤明显改善,凋亡细胞数显著减少(P<0.001),且与对照组相比无显著性差异(P>0.05),SOD显著升高(P<0.001),MDA显著降低(P<0.001)。结论给予外源性褪黑素可明显减少癫痫大鼠海马神经元凋亡,高剂量效果更佳,其作用机制可能涉及褪黑素对抗氧化应激反应,减轻神经元、线粒体损伤。Objective To investigate the effects of melatonin on oxidative stress and neuronal apoptosis in hippocampus of epileptic rats and the mechanism. Methods Seventy-two adult male Sprague-Dawley rats were equally divided into control group, model group, low dose group and high dose group. The model group was injected coriamyrtin 50 μg/kg in the lateral ventricle, while the low dose group and high dose group were injected melatonin 20 mg/kg and 60 mg/kg, respectively, 30 minutes before injection of coriamyrtin. The contents of malondialdehyde（MDA） and superoxide dismutase（SOD） were detected with ultraviolet spectrophotometer, the apoptosis was detected with TUNEL, and the ultrastructural changes of neurons and mitochondria in hippocampal CA3 region were observed with electron microscopy, after 60 minutes of epilepsy. Results The neurons and mitochondria in hippocampus were damaged, the number of apoptotic cells significantly increased（P0.001）, the content of SOD decreased（P0.001）, and the content of MDA increased（P0.001） in the model group, compared with the control group. In the low dose group, the ultrastructural damage relieved, the number of apoptotic cells decreased（P0.01）,the content of SOD increased（P0.05）, and the content of MDA decreased（P0.05）; and for the high dose group, the ultrastructural damage relieved very much, the number of apoptotic cells decreased（P0.001） and was not significantly different from the control group（P0.05）,SOD increased（P0.001）, and MDA decreased（P0.001）, compared with the model group. Conclusion Exogenous melatonin may significantly reduce neuronal apoptosis in rat hippocampal after epilepsy, and high dose is more effective, which may relate with resistance of oxidative stress, alleviate neuronal mitochondrial damage.

关 键 词：癫痫 褪黑素 氧化应激 凋亡 超微结构 大鼠 

分 类 号：R742.1[医药卫生—神经病学与精神病学]